SARS-CoV-2 and male infertility: from short- to long-term impacts.

PURPOSE: The coronavirus 2019 (COVID-19) pandemic-caused by a new type of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-has posed severe impacts on public health worldwide and has resulted in a total of > 6 million deaths. Notably, male patients developed more complications and had mortality rates ~ 77% higher than those of female patients. The extensive expression of the SARS-CoV-2 receptor and related proteins in the male reproductive tract and the association of serum testosterone levels with viral entry and infection have brought attention to COVID-19's effects on male fertility. METHODS: The peer-reviewed articles and reviews were obtained by searching for the keywords SARS-CoV-2, COVID-19, endocrine, spermatogenesis, epididymis, prostate, and vaccine in the databases of PubMed, Web of Science and Google Scholar from 2020-2022. RESULTS: This review summarizes the effects of COVID-19 on the male reproductive system and investigates the impact of various types of SARS-CoV-2 vaccines on male reproductive health. We also present the underlying mechanisms by which SARS-CoV-2 affects male reproduction and discuss the potentially harmful effects of asymptomatic infections, as well as the long-term impact of COVID-19 on male reproductive health. CONCLUSION: COVID-19 disrupted the HPG axis, which had negative impacts on spermatogenesis and the epididymis, albeit further investigations need to be performed. The development of vaccines against various SARS-CoV-2 variations is important to lower infection rates and long-term COVID risks.

Implementation of ovarian tissue cryopreservation in Hong Kong.

INTRODUCTION: Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. METHODS: This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. RESULTS: After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. CONCLUSION: This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Human varicella zoster virus is not present in the semen of a man affected by chickenpox during the in vitro fertilisation of his wife.

Human varicella zoster virus (VZV) is a member of the herpes virus family and affects humans only. Information about the presence of the virus in the semen samples of men affected by chickenpox is rather limited in the literature. Here, we reported a husband was affected by VZV during in vitro fertilisation treatment of his wife treated in our centre. The semen sample was checked for the presence of VZV by the PCR technique. The PCR result found no detectable viral DNA in the semen sample. The semen sample was then used for conventional IVF insemination and subsequently a healthy baby boy was born. This single case report suggests that the semen sample of men affected by chickenpox may be safe to use for assisted reproduction methods during the VZV infective period.

Trends of incidence, mortality and survival of multiple myeloma in Spain. A twenty-three-year population-based study.

BACKGROUND: Despite major advances, multiple myeloma remains an incurable disease. Epidemiological data from high-quality population-based registries are needed to understand the heterogeneous landscape of the disease. METHODS: Incidence, mortality and survival in multiple myeloma were comprehensively analyzed in the Girona and Granada population-based cancer registries, over a 23-year study (1994-2016), divided into three periods (1994-2001, 2002-2009 and 2010-2016). Joinpoint regression analysis was used to estimate the annual percentage change in incidence and mortality. Age-standardized net survival was calculated with the Pohar-Perme method. RESULTS: 1957 myeloma patients were included in the study, with a median age of 72 years. Age-standardized incidence and mortality rates decreased over time in both sexes and both rates were higher in males. Five-year age-standardized net survival by period was 27.4% (1994-2001), 38.8% (2002-2009), and 47.4% (2010-2016). Survival improved for all age groups: 32.4%, 74.1% and 78.5% for patients aged 15-49; 27.5%, 44.6%, and 58.5% for those aged 50-69; finally, 24.8%, 25.5%, and 26.3% for the older group. CONCLUSION: Incidence remained overall stable throughout the study, with only a small increase for men. Mortality was progressively decreasing in both sexes. Both incidence and mortality were higher in men. Age plays a critical role in survival, with impressive improvement in patients younger than 70 years, but only a minor benefit in those older than 70.

Trends of incidence, mortality and survival of multiple myeloma in Spain. A twenty-three-year population-based study

Background Despite major advances, multiple myeloma remains an incurable disease. Epidemiological data from high-quality population-based registries are needed to understand the heterogeneous landscape of the disease. Methods Incidence, mortality and survival in multiple myeloma were comprehensively analyzed in the Girona and Granada population-based cancer registries, over a 23-year study (1994–2016), divided into three periods (1994–2001, 2002–2009 and 2010–2016). Joinpoint regression analysis was used to estimate the annual percentage change in incidence and mortality. Age-standardized net survival was calculated with the Pohar–Perme method. Results 1957 myeloma patients were included in the study, with a median age of 72 years. Age-standardized incidence and mortality rates decreased over time in both sexes and both rates were higher in males. Five-year age-standardized net survival by period was 27.4% (1994–2001), 38.8% (2002–2009), and 47.4% (2010–2016). Survival improved for all age groups: 32.4%, 74.1% and 78.5% for patients aged 15–49; 27.5%, 44.6%, and 58.5% for those aged 50–69; finally, 24.8%, 25.5%, and 26.3% for the older group. Conclusion Incidence remained overall stable throughout the study, with only a small increase for men. Mortality was progressively decreasing in both sexes. Both incidence and mortality were higher in men. Age plays a critical role in survival, with impressive improvement in patients younger than 70 years, but only a minor benefit in those older than 70 (AU)